Functional biochemical compartmentilization in aspiny neurons

神经细胞通过称为突触的微小接触相互连接。大脑中的大多数兴奋性突触形成了高度专业化的细胞结构，称为树突。人们普遍认为，每个脊椎至少形成一个突触，代表着一个独立于相邻突触运作的独特的生化间隔。令人惊讶的是，大脑中大约三分之一的神经元没有脊椎，直接接受兴奋性传入到树突干上。虽然这种情况下的信号转导假定单个突触之间存在一定程度的串扰，但这种情况并没有发生，而且突触之间的通信仍然局限于激活的突触，而不影响邻近的突触。这就提出了一个重要的问题：Aspine神经元如何完成扩散隔离和突触特异性的信号转导？我们认为，不同传入细胞形成的突触具有特定的突触后功能生化区划机制，从而产生具有特定性质和不同生理作用的信号微域。为了确定突触后钙区域化的突触特异性机制，我们将研究海马CA1篮细胞中两种兴奋性突触的突触后钙信号：由Schaffer侧支支配的突触和穿支路径。将结合双光子显微镜、电生理学、药理学和分子技术来评估不同突触内突触后钙信号的时空分布及其调节和生理意义。

Nerve cells are connected to each other by tiny contacts, called synapses. The majority of excitatory synapses in the brain are formed onto highly specialized cellular structures known as dendritic spines. It is generally accepted that every spine forms at least one synapse and represents a distinct biochemical compartment operating independently from neighboring synapses. Surprisingly, about one third of neurons in the brain lack spines and receive excitatory afferents directly onto the dendritic shaft. While signal transduction in this case presumes a certain degree of cross talk among individual synapses, this does not happen and synaptic communication in aspiny neurons remains confined to activated synapses without affecting neighboring ones. This raises an important question: that is, how may aspiny neurons accomplish diffusionally isolated and synapse-specific signal transduction? We propose that synapses formed by different afferents possess specific postsynaptic mechanisms for functional biochemical compartmentalization, which produce signaling microdomains with specific properties and distinct physiological roles. To determine the synapse-specific mechanisms of postsynaptic calcium compartmentalization in aspiny neurons, we will examine postsynaptic Ca2+ signals at two types of excitatory synapses of hippocampal CA1 basket cells: synapses innervated by the Schaffer collaterals and the perforant path. A combination of two-photon microscopy, electrophysiology, pharmacology, and molecular techniques will be used to assess the spatio-temporal profile of postsynaptic Ca2+ signals within different synapses as well as their regulation and physiological significance.